Inclusion Criteria:
1. Voluntarily sign the written informed consent form and agree to participate in this study;
2. Pathologically confirmed esophageal squamous cell carcinoma;
3. Staged as T2-4bN0-3M0 or TXNXM1 (with supraclavicular lymph node metastasis), diagnosed as unresectable locally advanced esophageal cancer (according to the American Joint Committee on Cancer (AJCC) 8th edition);
4. Aged 18-75 years, male or female;
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
6. No prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy, surgery, etc.;
7. Adequate major organ function, meeting the following laboratory criteria:
Complete blood count: Neutrophil count ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L; Blood biochemistry: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min; Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
8. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study drug, and must use effective contraception during the study period and for at least 3 months after the last dose; Male patients with female partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study period and for 3 months after the last dose.
Exclusion Criteria:
1. Prior or concurrent treatment with any of the following:
1. Any prior or ongoing radiotherapy, chemotherapy, or other anti-tumor agents for malignancy;
2. Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes (at a dose \> 10 mg/day of prednisone or equivalent) within 2 weeks prior to the first dose of study drug. Inhaled or topical corticosteroids, and adrenal hormone replacement at doses \> 10 mg/day prednisone or equivalent, are permitted in the absence of active autoimmune disease;
3. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of study drug;
4. Major surgery or severe trauma within 4 weeks prior to the first dose of study drug;
2. Tumor-related exclusion criteria:
1. Non-esophageal cancer patients;
2. Patients without unresectable locally advanced or metastatic esophageal cancer;
3. Diagnosis of another malignancy within 5 years prior to the first dose of study drug, with the exception of cured cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer treated with radical surgery, and ductal carcinoma in situ treated with radical surgery;
3. Other criteria:
1. Poorly controlled cardiac symptoms or diseases, including: a) New York Heart Association (NYHA) class ≥ 2 heart failure; b) Unstable angina; c) Myocardial infarction within 1 year; d) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
2. Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). Patients with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be included; asthma requiring bronchodilators for medical intervention is excluded;
3. Pregnant or breastfeeding women;
4. History of severe allergic reactions to monoclonal antibodies, platinum agents, paclitaxel, or human serum albumin;
5. Human immunodeficiency virus (HIV)-positive patients, or patients with active hepatitis (hepatitis B reference: hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA (HBV DNA) ≥ 2000 IU/mL or ≥ 10⁴ copies/mL; hepatitis C reference: hepatitis C virus (HCV) antibody positive), or active pulmonary tuberculosis;
6. Any other condition that, in the investigator's judgment, may necessitate premature termination from the study.
